Preliminary study on the clinical value of noninvasive prenatal testing of fetal chromosomal copy number variations

Dong-mei LI; Hong-yun Zhang; Xin-hua Tang; Jin-man Zhang; Jie SU; Kai-yuan LI; Yong-mei Xia; Li-jian Zhao; Bao-sheng Zhu

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Preliminary study on the clinical value of noninvasive prenatal testing of fetal chromosomal copy number variations

Author: Dong-mei LI ¹ ; Hong-yun ZHANG ¹ ; Xin-hua TANG ¹ ; Jin-man ZHANG ¹ ; Jie SU ¹ ; Kai-yuan LI ¹ ; Yong-mei XIA ¹ ; Li-jian ZHAO ¹ ; Bao-sheng ZHU ¹
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1. Department of Obstetrics and Gynecology,Department of Genetic Diagnosis Center,Workstation of Academician Huanming YANG in Yunnan Province,Western Key Laboratory for Preconception Health Birth of State Commission of Health of China,First People's Hospital of Yunnan Province,Affiliated Hospital of Kunming University of Science and Technology Kunming 650032,China
Publication Type:Journal Article
Keywords: non-invasive prenatal testing; copy number variations; microdeletion/microduplication syndrome; prenatal diagnosis
From: Chinese Journal of Practical Gynecology and Obstetrics 2019;35(05):554-559
CountryChina
Language:Chinese
Abstract: OBJECTIVE: To explore the clinical value of non-invasive prenatal testing(NIPT)for screening fetal chromosomal copy number variations(CNVs) and microdeletion/microduplication syndromes(MDs).METHODS: Retrospective analysis was made in the 10 005 women who received NIPT during the first trimester(15-20+ 6 weeks)from January,2012 to July,2017,at First People's Hospital of Yunnan Province,Department of Genetic Diagnosis Center.Among them 32 pregnant women were indicated fetal CNVs,25 of 32 pregnant women selected interventional prenatal diagnosis.Statistical analysis was made on the amniotic fluid/cord blood chromosome G band karyotype and high-throughput sequencing(NGS)genome copy number analysis was made,and relevant CNVs were searched and analyzed in the corresponding database;the consistency of CNVs found in NIPT with interventional prenatal diagnosis was statistically analyzed.RESULTS: During the second trimester(15-20+ 6 weeks),in the 10 005 pregnant women who received NIPT testing 32 cases were shown to have high risks of fetal CNVs,and the screening positive rate was 0.32%(32/10 005).In 25 high risk pregnant women who accepted invasive prenatal diagnosis via informed choice,14 women wereconfirmed as fetal CNVs,the positive predictive value(PPV)of NIPT being 56%(14/25),including 9 cases of microdeletion and 5 cases of microduplication.The sizes were between 587.75 kb and 36.05 Mb.The size and the start and end positions of CNVs found by NIPT were similar to those of fetal DNA samples detected by NGS.Among 14 cases of fetal CNVs,11 cases were identified as MDs,3 cases as unknown clinical significance.In 11 cases of MDs,8 cases were observed fetal chromosome structure abnormalities by karyotype analysis,10 cases were confirmed as de novo abbreviations,and 2 cases as originated from paternal same MD.After genetic counseling,10 pregnant women in 11 cases of MDs chose informed terminations,and one case chose continuing pregnancy.CONCLUSION: As a high-precision screening method,NIPT is expected to be an effective mean to screen for fetal CNVs,which can be used to detect highrisk chromosome microdeletion and microduplication CNVs of larger segments.High risk cases of fetal CNVs found by NIPT require invasive prenatal diagnosis for validation.